This project will permit detailed study and correlation of the contractile or relaxant response of pulmonary vascular smooth muscle to selected agonists and antagonists and related biochemical properties of adrenergic receptors in pulmonary vascular smooth muscle. Three levels of pulmonary vascular tissue integration will be used. 1) In membrane fractions of homogenates we will measure specific binding of radioligands to adrenergic receptors, adenylate cyclase activity as well as altered cyclic nucleotide concentrations in response to adrenergic agents. 2) Intact, paired pulmonary vascular strips will be used to assess the pharmacological response to a series of adrenergic agonists or antagonists each used over a concentration range which will allow plotting of concentration-effect curves and interpolation of EC50 values. In similar preparations, we will measure adrenergic radioligand binding affinities and adenylate cyclase activities and cyclic nucleotide concentrations. 3) We will also evaluate receptor binding of radioligand in paired, independently perfused rabbit lungs. These three types of evaluation of adrenergic receptor functional properties will be carried out in tissue from untreated rat, rabbit and guinea pig and will be compared with tissue obtained from human lung removed during cardio-thoracic surgery. Similar studies will be carried out with tissue from animals pre-treated with drugs which modify vascular tone by various mechanisms. These drugs include reserpine, 6-hydroxydopamine, Aminorex and monocrotaline. Data generated in this study will provide basic information on the molecular pharmacology of adrenergic receptors in pulmonary vascular muscle. Such information will contribute to fundamental understanding of this important aspect of pulmonary vascular control and is also an essential prerequisite to understanding both the pathological modification of pulmonary vascular tone such as that in pulmonary hypertension, and its pharmacological treatment.